Injection is the most commonly used method for administering vaccines and protein therapeutics, such as insulin, to humans. However, injection therapies have numerous drawbacks such as discomfort to the patient, poor patient compliance, and the need for administration by trained technicians.
A desired alternative method of immunization would be intranasal administration of a composition containing a therapeutically effective amount of an antigen. The intranasal route may be suited to mass vaccination, given the simplicity of the delivery systems, their ease of use, and minimal invasiveness. Many pathogens infect via the respiratory mucosa; therefore, immunization at these mucosal sites can be more efficacious than immunization by injection.
However, intranasal delivery of antigens, many of them being macromolecules such as peptides or proteins, have had limited success because the antigens are not particularly effective in penetrating the mucous membrane of the nasal passage, and because the tendency of some permeation agents to irritate those membranes.
Anthrax is an infection caused by the spore-forming bacterium Bacillus anthracis. Anthrax may enter the body and cause infection by means of inhalation, ingestion or subcutaneous exposure. Recent heightened awareness of the possibility of bioterrorism has raised concerns about the use of B. anthracis or related strains, both newly emerging or genetically engineered, as bio-weapons. Anthrax protective antigen (PA) has been administered intranasally as a liquid in mice and has provided protection against aerosol challenge in murine models. Flick-Smith et al. Mucosal or parenteral administration of microsphere-associated Bacillus anthracis protective antigen protects against anthrax infection in mice. Infect. Immun. 2002; 70:2022-8. Gaur et al. Effect of nasal immunization with protective antigen of Bacillus anthracis on protective immune response against anthrax toxin. Vaccine 2002; 20: 2836-9. Boyaka et al. Effective mucosal immunity to anthrax: neutralizing antibodies and Th cell responses following nasal immunization with protective antigen. J. Immunol. 2003; 170: 5636-43.
There still remains a need for an effective and safe vaccine that would effectively produce immunity to anthrax with fewer doses.
By using permeation enhancers, the present invention provides compositions and methods for efficient nasal immunization against various antigens, including anthrax. The ability to confer protection following intranasal delivery is particularly attractive in the context of a bioterrorism event as it would greatly simplify the process of mass vaccinations. The present invention includes within its scope also the intranasal method of delivering peptides, peptidomimetics and proteins in general for therapeutic purposes.